TY - JOUR
T1 - Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death
AU - Byrne, Alicia B.
AU - Arts, Peer
AU - Ha, Thuong T.
AU - Kassahn, Karin S.
AU - Pais, Lynn S.
AU - O'Donnell-Luria, Anne
AU - Broad Institute Center for Mendelian Genomics, null
AU - Babic, Milena
AU - Frank, Mahalia S. B.
AU - Feng, Jinghua
AU - Wang, Paul
AU - Lawrence, David M.
AU - Eshraghi, Leila
AU - Arriola, Luis
AU - Toubia, John
AU - Nguyen, Hung
AU - Genomic Autopsy Study Research Network, null
AU - Edwards, Matt
AU - McGillivray, George
AU - Pinner, Jason
AU - McKenzie, Fiona
AU - Morrow, Rebecca
AU - Lipsett, Jill
AU - Manton, Nick
AU - Khong, T. Yee
AU - Moore, Lynette
AU - Liebelt, Jan E.
AU - Schreiber, Andreas W.
AU - King-Smith, Sarah L.
AU - Hardy, Tristan S. E.
AU - Jackson, Matilda R.
AU - Barnett, Christopher P.
AU - Scott, Hamish S.
PY - 2023/1
Y1 - 2023/1
N2 - Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies.
AB - Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies.
UR - http://hdl.handle.net/1959.7/uws:69721
U2 - 10.1038/s41591-022-02142-1
DO - 10.1038/s41591-022-02142-1
M3 - Article
SN - 1078-8956
VL - 29
SP - 180
EP - 189
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -
